82 articles - From Saturday Jan 29 2022 to Friday Feb 04 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Lancet Haematol |
Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Given that infectious risk is cumulative through the course of the disease, preventing infections is paramount. Optimal preventive strategies include vaccination against common pathogens, antimicrobial prophylaxis, infection control measures, and immunoglobulin replacement in a small subset of patients; however, there are no universally accepted guidelines for infection prevention. This Review provides a consensus statement from a panel of 36 experts with global representation, which was convened by The International Myeloma Society to review existing literature and current guidelines, address issues associated with the risk of infection and prevention of infectious complications in multiple myeloma in the context of emerging therapies, and offer recommendations for preventing these complications. |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Anti-CD19 and anti-BCMA CAR T cell therapy followed by lenalidomide maintenance after autologous stem-cell transplantation for high-risk newly diagnosed multiple myeloma. Although the sample size was small and there was a lack of control in this single-arm study, the clinical benefits observed warrant ongoing randomized controlled trials. (NCT03455972). |
Cerebral Oxygen Metabolic Stress is Increased in Children with Sickle Cell Anemia Compared to Anemic Controls. While infarcts colocalized within regions of elevated OEF, more SCA participants had infarcts than AC (p<0.001). We conclude that children with SCA experience elevated OEF compared to AC and HC after controlling for the impact of anemia, suggesting that there are other pathophysiologic factors besides anemia contributing to cerebral metabolic stress in children with SCA. |
Chronic neutrophilic leukemia: 2022 update on diagnosis, genomic landscape, prognosis, and management. Disease updates Increasingly comprehensive genetic profiling in CNL, including new data on clonal evolution, has disclosed a complex genomic landscape with additional mutations and combinations thereof driving disease progression and drug resistance. Though accurate prognostic stratification and therapeutic decision-making remain challenging in CNL, emerging data on molecular biomarkers and the addition of newer agents, such as JAK inhibitors, to the therapeutic arsenal, are paving the way towards greater standardization and improvement of patient care. |
Health-related quality of life in patients with relapsed/refractory multiple myeloma treated with pomalidomide and dexamethasone ± subcutaneous daratumumab: patient-reported outcomes from the APOLLO trial. Overall, these results suggest patients' health-related quality of life remained stable when daratumumab was added to Pd, with several results favoring D-Pd versus Pd. These findings complement the significant clinical improvements observed with D-Pd and support its use in patients with RRMM. |
| Ann Oncol |
Baseline computed tomography screening and blood microRNA predict lung cancer risk and define adequate intervals in the BioMILD trial. The combined use of LDCT and blood microRNAs at baseline predicts individual LC incidence and mortality, with a major effect of MSC for LDCT-positive individuals. These findings may have important implications in personalizing screening intervals. |
European cancer mortality predictions for the year 2022 with focus on ovarian cancer. We predicted additional declines in cancer mortality rates for 2022. The slowdown in female lung cancer mortality reflects some levelling of smoking in women. Favourable ovarian cancer trends are likely to continue and are largely attributable to the spreading oral contraceptive use and some impact of improved diagnosis and management. |
Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase 3 trial. Improvement in pCR with addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, while adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by AC neoadjuvant chemotherapy for early stage TNBC. |
| Blood |
A Mechanism for Hereditary Angioedema Caused by a Lysine311 to Glutamic Acid Substitution in Plasminogen. Substantial BK generation occurs during Plm-Glu311 cleavage of human HK, but not mouse HK. Furthermore, mouse plasmin, which has Glu311, did not liberate bradykinin from human kininogens more rapidly than human Plg-Lys311. This indicates Glu311 is pathogenic in the context of human plasmin when human kininogens are the substrates. |
Disrupting the adult-globin promoter alleviates promoter competition and reactivates foetal-globin gene expression. In al cases where foetal globin is up-regulated, the proximal adult b-globin (HBB) promoter is deleted. We use CRISPR gene editing to delete or disrupt elements within the promoter and find that virtually al mutations that reduce HBB promoter activity, result in elevated foetal globin expression. These results fit with previous models where the foetal and adult globin genes compete for the distal Locus Control Region and suggest that targeting the HBB promoter might be explored to elevate foetal globin and reduce sickle globin expression as a treatment for b-haemoglobinopathies. |
Fetal versus adult megakaryopoiesis. Over the last few years, studies have challenged traditional paradigms about the origin of the megakaryocyte lineage in both fetal and adult life, and the application of single-cell RNA sequencing has led to a better characterization of embryonic, fetal and adult megakaryocytes. In particular, a growing body of data suggest that -at al stages of development- the various functions of megakaryocytes are not fulfilled by the entire megakaryocyte population as a whole, but rather by distinct megakaryocyte sub-populations with dedicated roles. Finally, recent studies have provided novel insights into the mechanisms underlying developmental disorders of megakaryopoiesis, which either uniquely affect fetuses and neonates or have different clinical presentations in neonatal compared to adult life. |
Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT inborn errors working party analysis. The overall cumulative incidences of grade III-IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure, mixed donor chimerism and more frequently received secondary procedures (2nd HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age =5 years remains a risk factor for overall survival. |
Impaired p47phox phosphorylation in neutrophils from p67phox-deficient chronic granulomatous disease patients. In vitro studies showed that recombinant p47phox was phosphorylated on Ser304, Ser315, Ser320 and Ser328 by different PKC isoforms and the addition of recombinant p67phox alone or in combination with p40phox potentiated this process. Thus, p67phox and p40phox are required for optimal p47phox phosphorylation on Ser304, Ser315, Ser320 and Ser328 in intact cells. Therefore, p67phox and p40phox are novel regulators of p47phox-phosphorylation. |
MOLECULAR CHARACTERIZATION OF MUTANT TP53 ACUTE MYELOID LEUKEMIA AND HIGH-RISK MYELODYSPLASTIC SYNDROME. Detection of residual mutant TP53 was not associated with survival. In conclusion, mutant TP53 AML and MDS-EB do not differ with respect to molecular characteristics and survival. Therefore, mutant TP53 AML/MDS-EB should be considered a distinct molecular disease entity. |
Most Anti-PF4 Antibodies in Vaccine-induced Immune Thrombotic Thrombocytopenia are transient. None of the 29 VITT patients who received a second vaccination dose with an mRNA COVID-19 vaccine developed new thromboses or relevant increase in anti-PF4/heparin IgG EIA OD, regardless whether PF4-dependent platelet-activating antibodies were still present. PF4-dependent platelet-activating antibodies are transient in most patients with VITT. VITT patients can safely receive a second COVID-19 mRNA-vaccine shot. |
Phase 2 study of obinutuzumab (GA-101), ibrutinib and venetoclax (CLL2-GIVe) in patients with untreated high-risk chronic lymphocytic leukemia. Adverse events were reported in al patients, most were low grade (grade =3: 23.9%). Two deaths were reported (cardiac failure and ovarian carcinoma), neither related to study treatment. The CLL2-GIVe treatment regimen has a manageable safety profile and is a first-line treatment of good efficacy for patients with high-risk CLL. |
Pivotal role of PIM2 kinase in plasmablast generation and plasma cell survival, opening new treatment options in myeloma. In PCs, interleukin-6 triggered PIM2 expression, resulting in anti-apoptotic effects on which malignant PCs were particularly dependent. In multiple myeloma, pan-PIM and MCL1 inhibitors displayed synergistic activity. Our results highlight a cell-autonomous function that links kinase activity to the PBs' newly acquired secretion ability and the adaptability observed in both normal and malignant PCs, and finally should prompt the reconsideration of PIM2 as a therapeutic target in multiple myeloma. |
Targeting Cancer-Associated Fibroblasts in the Bone Marrow Prevents Resistance to CART-Cell Therapy in Multiple Myeloma. To overcome CAF-induced CART-cell inhibition, we generated CART cells targeting both MM cells and CAFs. Our dual-targeting CART-cell strategy significantly improved the effector functions of CART cells. We demonstrate for the first time that dual targeting both malignant plasma cells and the CAFs within the TME is a novel strategy to overcome resistance to CART-cell therapy in MM. |
| Blood Adv |
Analysis of Racial and Ethnic Disparities in Multiple Myeloma U.S. FDA Drug Approval Trials. S. patients were more favorable compared to patients in the RoW. Given the higher incidence of MM in AA and different disease characteristics, efforts should be made to improve representation of AA in MM clinical trials. |
Deleterious effect of bone marrow-resident macrophages on hematopoietic stem cells in response to total body irradiation. Pharmacological or genetic depletion of bone marrow resident macrophages impairs the radio-induced increases in the percentage of both ROS+ LT-HSC and peroxynitrite+ LT-HSC and results in a complete recovery of a functional pool of LT-HSC. Finally, we show that after a 2 Gy-TBI, a specific decrease of NO production by bone marrow resident macrophages improves the LT-HSC recovery, whereas an exogenous NO delivery decreases the LT-HSC compartment. Altogether, these results show that bone marrow resident macrophages are involved in the response of LT-HSC to a 2 Gy-TBI and suggest that regulation of NO production can be used to modulate some deleterious effects of a TBI on LT-HSC. |
Deletion of Y-chromosome before allogeneic hematopoietic stem cell transplantation in male recipients with female donors. On the other hand, the Del(Y) group was not significantly associated with any clinical outcomes in the cohort of male-to-male allo-HCT. A higher incidence of relapse might be caused by attenuation of the GVL due to a lack of H-Y antigens. Since a GVL due to a sex-mismatch itself may not be expected in male recipients with Del(Y) who receive allo-HCT from a female donor, additional post-allo-HCT strategies might be required to prevent disease relapse. |
Improving eligibility criteria for first-line trials for patients with DLBCL using a U.S.-based Delphi-method survey. We then surveyed lymphoma clinical trial experts representing eight academic medical centers in the United States regarding essential and unnecessary eligibility criteria for modern DLBCL RCTs. Seventeen of 29 invited clinical investigators completed the round-one questionnaire (response rate of 58.6%), 15 of 17 round-one participants (88.2%) completed the round-two survey, and al round-one participants reviewed finalized recommendations for eligibility criteria for modern first-line DLBCL RCTs. We defined consensus recommendations for 31 modernized eligibility criteria including threshold values for 10 quantitative eligibility criteria aimed at facilitating enrollment of a clinically diverse study population in first-line DLBCL RCTs designed to improve standard of care therapy. |
Quantitative analysis of mRNA-1273 COVID-19 vaccination response in immunocompromised adult hematology patients. Serum IgG4, absolute B and NK cell number and number of immunosuppressants predicted S1 IgG =300 BAU/ml. Hematology patients on chemotherapy, shortly after HCT, or with chronic GvHD should not be precluded from vaccination. Netherlands Trial Register NL9553. |
Scheduled Administration of Virus-Specific T cells for Viral Prophylaxis After Pediatric Allogeneic Stem Cell Transplant. No infusion reactions occurred. In conclusion, scheduled VSTs appear to be safe and potentially effective at limiting serious complications from viral infections after allogeneic transplantation. A randomized study comparing this scheduled approach to the use of VSTs to treat active viremia is ongoing. |
| Blood Cancer J |
A simple additive staging system for newly diagnosed multiple myeloma. Among 1327 evaluable patients, OS was 11.0 (95% |
Azacitidine-induced reconstitution of the bone marrow T cell repertoire is associated with superior survival in AML patients. The favorable broadening of the BM T cell space appeared to be driven by antigen since these patients showed significant skewing of TRBV gene usage. Our data suggest that one course of AZA can cause reconstitution to a more physiological T cell BM niche and that the T cell space plays an underestimated prognostic role in AML. Trial registration: DRKS identifier: DRKS00004519. |
Chronic lymphocytic leukemia (CLL) with Reed-Sternberg-like cells vs Classic Hodgkin lymphoma transformation of CLL: does this distinction matter? The median overall survival (OS) of patients with CLL-HRS was 17.5 |
Determining clinical course of diffuse large B-cell lymphoma using targeted transcriptome and machine learning algorithms. Using the expression levels of 180 genes, our model reliably predicted the four survival subgroups and was validated using independent groups of patients. Multivariate analysis showed that this patient stratification strategy encompasses various biological characteristics of DLBCL, and only TP53 mutations remained an independent prognostic biomarker. This novel approach for stratifying patients with DLBCL, based on the clinical outcome of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, can be used to identify patients who may not respond well to these types of therapy, but would otherwise benefit from alternative therapy and clinical trials. |
Genomic characterization of functional high-risk multiple myeloma patients. FHR patients are characterized by increased mutations affecting the IL-6/JAK/STAT3 pathway, and a gene expression profile associated with aberrant mitosis and DNA damage response. This is also corroborated by the association with the mutational signature associated with abnormal DNA damage response. We have also developed a machine learning based classifier that can identify most of these patients at diagnosis. |
Myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T): Mayo-Moffitt collaborative study of 158 patients. In univariate analysis, age =70 years (P |
Patients in complete remission after R-CHOP(-like) therapy for diffuse large B-cell lymphoma have limited excess use of health care services in Denmark. DLBCL survivors had on average 10.3 (9.3-11.3) inpatient bed days within 5 years of response evaluation, whereas matched comparators had 8.4 (7.9-8.8). The rate of outpatient visits was also significantly higher(excluding routine follow-up visits, incidence rate ratio, 1.3, P |
| Haematologica |
Temsirolimus combined with cyclophosphamide and etoposide for pediatric patients with relapsed/refractory acute lymphoblastic leukemia: a Therapeutic Advances in Childhood Leukemia Consortium trial (TACL 2014-001). Responses were observed across al DLs. Pharmacodynamic mTOR target inhibition was achieved and appeared to correlate with temsirolimus dose. Future testing of next-generation PI3K/mTOR pathway inhibitors with chemotherapy may be warranted to increase response rates in children with relapsed/refractory ALL. |
YTHDF3 modulates hematopoietic stem cells by recognizing RNA m6A modification on Ccnd1. Ythdf3 and Mettl3 regulates HSCs by transmitting m6A RNA methylation on the 5'UTR of Ccnd1. Enforced Ccnd1 completely rescues the defect of Ythdf3-/- HSCs and partially rescues Mettl3-compromised HSCs. Taken together, this study for the first time identified that Ccnd1 is the target of METTL3 and YTHDF3 to transmit m6A RNA methylation signal to regulate HSCs reconstitution capacity. |
| J Hematol Oncol |
Impact of frontline treatment approach on outcomes in patients with secondary AML with prior hypomethylating agent exposure. The outcomes of ts-AML are poor but may be improved with use of an HMA plus venetoclax-based regimen, followed by HSCT, particularly in those with a non-adverse risk karyotype. |
| Lancet Haematol |
Individualised dosing of anti-thymocyte globulin in paediatric unrelated allogeneic haematopoietic stem-cell transplantation (PARACHUTE): a single-arm, phase 2 clinical trial. Interpretation Individualised dosing of anti-thymocyte globulin led to a significant improvement in early CD4 + immune reconstitution without increasing GVHD and graft failure incidence. Promotion of early CD4 + immune reconstitution by individualising anti-thymocyte globulin dose might improve outcomes of allogeneic HSCT. Funding Sanofi. |
KIR2DS1-HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials. Interpretation Assessment of KIR2DS1 and HLA-C genotype might identify patients who would not benefit from rituximab, thereby allowing alternative therapies to be given. Further validation of these findings in prospective clinical trials is needed. Funding F Hoffman La Roche. |
| Leukemia |
CDK19 regulates the proliferation of hematopoietic stem cells and acute myeloid leukemia cells by suppressing p53-mediated transcription of p21. Further investigations show that CDK19 can interact with p53 to inhibit p53-mediated transcription of p21 in HSCs and treatment with a specific p53 inhibitor (PFTß) partially rescues the defects of CDK19-null HSCs. Importantly, SenexinB treatment markedly inhibits the proliferation of AML cells. Collectively, our findings indicate that CDK19 is involved in regulating HSC and AML cell proliferation via the p53-p21 pathway, revealing a new mechanism underlying cell cycle regulation in normal and malignant hematopoietic cells. |
Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancy and COVID-19: a longitudinal cohort and propensity score analysis. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20-exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI |
| Thromb Haemost |
Bleeding risk assessment in end-stage kidney disease: validation of existing risk scores and evaluation of a machine learning-based approach. Existing bleeding risk scores and a machine learning approach including common clinical parameters fail to assist in bleeding risk prediction of patients on HD. Therefore, new approaches, including novel biomarkers, to improve bleeding risk prediction in patients on HD are needed. |
DOAC Dipstick testing can reliably exclude the presence of clinically relevant DOAC concentrations in circulation. Visual analysis using the DOAC Dipstick was 100% in agreement with that of the optoeletronic DOASENSE Reader for al three DOACs. DOAC Dipstick testing can reliably exclude the presence of DOACs in urine samples at best fitting thresholds of >14 and >19 ng/mL in plasma. The performance of the DOAC Dipstick at detecting lower DOAC concentrations in plasma requires confirmation. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| Blood Cancer J |
| Lancet Haematol |
Malignancy-associated haemophagocytic lymphohistiocytosis. Mortality remains high with current approaches. Targeted therapy, including blockade of specific cytokines such as IL-1, IL-6, and IFN |
Risk stratified management approaches for smouldering multiple myeloma: clinical research becomes clinical practice. Ongoing uncertainties include the duration of therapy, acceptable risks, and intensity of treatment (curative vs preventive), al of which are being tested in ongoing trials. Finally, common methods for risk stratification are crucial for allowing comparison across trials, and the 20/2/20 (Mayo 2018) criteria might be one such method, on the basis of their simplicity and broad availability. A focus on phase 3 trials is key to moving the field forward in a way that answers these questions and ultimately improves outcomes for patients. |
| Leukemia |
Inflammation and infection in plasma cell disorders: how pathogens shape the fate of patients. the underlying disease status, patient age and comorbidities, and myeloma-directed treatment), with the aim of highlighting future prophylactic and preventive strategies that could be implemented in the clinic. Beyond this, infection and pathogens as an entity are believed to also influence disease biology from initiation to response to treatment and progression through a complex interplay involving pathogen exposure, chronic inflammation, and immune response. This review will outline both the direct and indirect role played by oncogenic pathogens in PCD, highlight the requirement for large-scale studies to decipher the precise implication of the microbiome and direct pathogens in the natural history of myeloma and its precursor disease states, and understand how, in turn, pathogens shape plasma cell biology. |
Selective inhibition of nuclear export: a promising approach in the shifting treatment paradigms for hematological neoplasms. Apart from the TSP cargo transport and its role in drug resistance, XPO1 inhibition results in retention of master transcription factors essential for cell differentiation, cell survival, and autophagy, rendering cells more susceptible to the effects of other antineoplastic agents, including targeted therapies. This review will dissect the role of XPO1 inhibition in hematological neoplasms, focusing on mechanistic insights gleaned mainly from work with SINE compounds. Future potential combinatorial strategies will be discussed. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
all remaining publications eg case reports, images of the month, etc…
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |